medRxiv preprint doi: https://doi.org/10.1101/2020.09.26.20189522; this version posted September 28, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . Clinical Course And Risk Factors For In-hospital Death In Critical COVID-19 In Wuhan, China Fei Li, MD, PhD1,2#, Yue Cai, MD1,2#, Chao Gao, MD, PhD1#, Lei Zhou, MD, PhD2,3#, Renjuan Chen, MD, PhD1, Kan Zhang, MD1,2, Weiqin Li, MD2,4, Ruining Zhang, MD1, Xijing Zhang, MD, PhD2,5, Duolao Wang, PhD 6*, Yi Liu, MD, PhD1*, Ling Tao, MD, PhD1* 1. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an, China 2. Huoshenshan Hospital, Wuhan, China 3. Clinical Laboratory, Xijing Hospital, Fourth Military Medical University, Xi’an, China 4. Department of Critical Care Medicine, Jinling Hospital, Nanjing, China 5. Surgical ICU, Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an, China 6. Department of Clinical Sciences Liverpool School of Tropical Medicine Pembroke, Liverpool, United Kingdom Address for correspondence: Professor Ling Tao, MD, PhD. Professor of Cardiology – Xijing hospital, Xi’an, China 127 Changle west road, Xi’an, 710032, China Email: [email protected] Professor Yi Liu, MD, PhD. Professor of Cardiology – Xijing hospital, Xi’an, China 127 Changle west road, Xi’an, 710032, China Email: liuyimeishan@hotmail,.com 1 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.09.26.20189522; this version posted September 28, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . Professor Xijing Zhang, MD, PhD. Professor of Anesthesia – Xijing hospital, Xi’an, China 127 Changle west road, Xi’an, 710032, China Email: [email protected] 2 medRxiv preprint doi: https://doi.org/10.1101/2020.09.26.20189522; this version posted September 28, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . BACKGROUND The risk factors for mortality of COVID-19 classified as critical type have not been well described. OBJECTIVES This study aimed to described the clinical outcomes and further explored risk factors of in-hospital death for COVID-19 classified as critical type. METHODS This was a single-center retrospective cohort study. From February 5, 2020 to March 4, 2020, 98 consecutive patients classified as critical COVID-19 were included in Huo Shen Shan Hospital. The final date of follow-up was March 29, 2020. The primary outcome was all-cause mortality during hospitalization. Multivariable Cox regression model was used to explore the risk factors associated with in-hospital death. RESULTS Of the 98 patients, 43 (43.9%) died in hospital, 37(37.8%) discharged, and 18(18.4%) remained in hospital. The mean age was 68.5 (63, 75) years, and 57 (58.2%) were female. The most common comorbidity was hypertension (68.4%), followed by diabetes (17.3%), angina pectoris (13.3%). Except the sex (Female: 68.8% vs 49.1%, P=0.039) and angina pectoris (20.9% vs 7.3%, P = 0.048), there was no difference in other demographics and comorbidities between non-survivor and survivor groups. The proportion of elevated alanine aminotransferase, creatinine, D-dimer and cardiac injury marker were 59.4%, 35.7%, 87.5% and 42.9%, respectively, and all showed the significant difference between two groups. The acute cardiac injury, acute kidney injury (AKI), and acute respiratory distress syndrome (ARDS) were observed in 42.9%, 27.8% and 26.5% of the patients. Compared with survivor group, non-survivor group had more acute cardiac injury (79.1% vs 14.5%, P<0.0001), AKI (50.0% vs 10.9%, P<0.0001), and ARDS (37.2% vs 18.2%, P=0.034). Multivariable Cox regression showed increasing hazard ratio of in-hospital death associated with acute cardiac injury (HR, 6.57 [95% CI, 1.89-22.79]) and AKI (HR, 2.60 [95% CI, 1.15-5.86]). 3 medRxiv preprint doi: https://doi.org/10.1101/2020.09.26.20189522; this version posted September 28, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . CONCLUSIONS COVID-19 classified as critical type had a high prevalence of acute cardiac and kidney injury, which were associated with a higher risk of in-hospital mortality. INTRODUCTION Beginning in December 2019, the COVID-19 has caused an international outbreak of respiratory illness. By March 30, 2020, the confirmed COVID-19 patients had exceeded 700 thousand. The soaring of COVID-19 has been seen as one of the most serious hazards to global health. COVID-19 is clinically classified as four types: mild, moderate, severe and critical. Critical patients have critical pulmonary injury, systemic inflammatory status and a very high mortality(1-3), which leads to tremendous difference in clinical course, medical intervention and prognosis compared with mild to severe type. Illustration of demographics, clinical characteristics, complications and treatment outcome of critical patients is practically important to get further insights into the early origins of adverse outcomes and may ultimately be relevant for developing clinical prediction models. Although some COVID-19 case series and studies have been reported previously(4-6), to our knowledge, there are limited studies only including critical patients and specifically focusing on adverse outcomes and the predictive factors. In the present study, we retrospectively included 98 consecutive patients with critical COVID-19 in Huoshenshan hospital (Wuhan, China). We described the patient demographics, laboratory findings, treatment & complications and further explored risk factors of in-hospital death for these patients. METHODS Study design and Participants This is a single-center, retrospective cohort study. A total of 2074 consecutive patients with COVID-19 were screened in Huo Shen Shan Hospital from February 5, 2020 to March 4, 2020. Huo Shen Shan Hospital was opened since February 3, 2020, designated by the government only for treating COVID-19. After excluding the mild, 4 medRxiv preprint doi: https://doi.org/10.1101/2020.09.26.20189522; this version posted September 28, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . moderate and severe patient, 98 patients classified as critical type on or after admission were included in the final analysis. The final follow-up date was March 29, 2020. Patients with COVID-19 enrolled in this study were diagnosed according to World Health Organization interim guidance (7). The classification of COVID-19 is according to the COVID-19 diagnosis and treatment program issued by the National Health Commission of China(8): (1) Mild type: mild symptoms, and no pneumonia imaging showed. (2) Moderate type: patients with fever, respiratory symptoms, and/or pneumonia imaging. (3) Severe type: patients with any of the following: shortness of breath, respiratory rate (RR)>30 times/ min; oxygen saturation <93% in resting state; Arterial partial pressure of oxygen / Fraction of inspired oxygen (PaO2/ FiO2）<300 mmHg（1mmHg=0.133 kPa) and the pulmonary imaging showed more than 50% lesion progression within 24 ~ 48h; (4) Critical type: patients with any of the following conditions: respiratory failure requiring mechanic ventilation, shock, or organ failure requiring intensive care. Patients were divided into Survivor Group or Non-survivor Group according to their clinical outcome. This study was approved by the National Health Commission of China and the institutional review board at Huoshenshan Hospital (HSSLL025). Written informed consent was waived by the Ethics Commission of the designated hospital for patients with emerging infectious diseases. Data Collection The demographics, laboratory findings, treatment & complications for participants during hospitalization were collected from electronic medical records by 2 investigators. All data were independently reviewed and entered into the computer database by 2 analysts. Clinical Endpoints 5 medRxiv preprint doi: https://doi.org/10.1101/2020.09.26.20189522; this version posted September 28, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . The primary endpoint was all-cause mortality during hospitalization. Other endpoints included: 1) Cardiac injury , defined as blood levels of cardiac injury markers (hs-TNI or CK-MB) above the upper reference limit.; 2)Acute respiratory distress syndrome (ARDS), defined according to the Berlin definition(9); 3)Acute kidney injury, identified according to the Kidney Disease: Improving Global Outcomes definition (KDIGO)(10). Statistical Analysis Continuous data are presented as mean SD or median (interquartile range) and compared using the Student’s t-test or the Mann-Whitney test depending on their distributions. Categorical variables were expressed as frequencies with percentages and compared with the Chi-square or Fisher exact tests as required.